as well. These drugs are toxic, have poor tissue selectivity, and continuously using them may increase resistance against them [38]. The toxicity of a drug is always a concern because most drugs are not tissue specific, i.e. they have the same effect on normal and abnormal cells. The use of nanotechnology makes it possible to have a specifically targeted drug delivery system. From size manipulation to creating various delivery vehicles, nanotechnology can help specifically to target and assemble in tumor cells [39].
1.2.2.1 Metal‐Based Drug Delivery
There are several metal‐based nanodrugs that have shown great success in treatments; however, they are known to produce large quantities of toxic and other harmful substances [40]. A way to lower the negative consequences of nanometal drugs is to modify their properties. For example, the study of biodegradable iron stents and cobalt‐chromium stents in porcine coronary arteries of juvenile pigs showed to have the potential to reduce chronic inflammation and premature recoil. Another study shows that modifying biocompatible and monodispersed iron oxide superparamagnetic nanoparticles with the combination of folic acid (FA) and polyethylene glycol (PEG) increased the affinity of nanoparticle uptake by targeted cells [41].
For antitumor therapy, two‐dimensional molybdenum disulfide (MoS₂) nanosheets have proved to be a good photothermal agent. An extensive study has shown that soybean phospholipid encapsulated MoS₂ nanosheets have shown good photothermal conversion performance and photothermal stability. In addition, soybean phospholipids can be found in nature, so the cost of obtaining it from natural resources is always lower than synthetically developing it. The reason MoS₂ nanosheets do not necessarily carry a drug to cancerous cells; however, as a photothermal agent, they can absorb near‐infrared reflectance (NIR) light and convert it into heat, which then can be transported to tumor cells. This process will bring the temperature to the critical temperature of 42 °C and result in efficient cell death. This was tested on mice with breast tumor growth by intravenously and intratumorally injecting soybean phospholipid molybdenum disulfide (SP‐MoS₂) nanosheets. Both methods showed suppression of growth of the tumor [42].
Metallic nanodrugs can also be used as antiseptics or for antimicrobial purposes. For example, hydrophilic metallic silver nanoparticle (AgNP) nanocomposites composed of a polymer matrix of N‐vinylpyrrolidone (poly [VT‐co‐VP]) have various uses in medicine especially as an ingredient in burn medicine. The study shows these metallic nanocomposites exhibiting antimicrobial activities toward Gram‐negative and Gram‐positive bacteria. Additionally, silver has shown to have more antimicrobial effect on Gram‐negative bacteria due to better linkage between the silver nanocomposites and the hydrophilic channels present in the outer membrane of Gram‐negative bacteria. In addition to antimicrobial properties, silver nanocomposites have shown to not precipitate or shrink when stored in an aqueous environment for four months. This is due to the stability of functional groups in the nanocomposites. It is proposed that these silver nanocomposites can be used for the treatment of various infectious diseases and can be quite useful after surgeries in which the major problems can be caused by exposure to bacteria [43].
1.2.2.2 Biotechnology‐Based Drug Delivery
There are various developments in drug delivery systems based on combinations of biomacromolecules and nanoparticles. Since drug delivery is popular in cancer treatment, most of the developments have occurred in oncology. For the treatment of malignant melanoma, folate‐decorated cationic liposomes have been developed as nonviral vectors of hypoxia‐inducible factor 1‐α siRNA (HIF‐1α siRNA). Hypoxia‐inducible factor 1‐α is a transcription factor that responds to hypoxic stress and could be a potential target in malignant melanoma therapy. When HIF‐1α is upregulated, transcription is activated that results in angiogenesis. Small interfering RNA (siRNA) are pieces of double‐stranded RNA that can interfere with the translation of proteins and inhibit angiogenesis when used against HIF‐1α. The double‐stranded RNA alone did not achieve the antiangiogenesis activity, thus HIF‐1α siRNA vector is an excellent vehicle that can load siRNA and protect it from degradation [44]. Another method of delivering anticancer drugs, such as quercetin, is a lecithin‐based mixed polymeric micelle. Although quercetin (Que) is a well‐known and successful anticancer drug, its low solubility and low oral bioavailability (BA) hinders its use in clinical settings. A micelle as a delivery system is quite useful in this case because its hydrophobic core and hydrophilic shell provide a safe passage for low soluble drugs. To increase the solubility of drugs, the more hydrophobic material is added to the micelle, which increases the space in the hydrophobic core and provides more space for drugs to be solubilized. Lecithin is a hydrophobic mixture of organic phospholipids that help in the absorption of drugs. In this case, lecithin helps increase the BA of Que. These micelles not only are able to increase drug solubility and BA but also, due to their nanosize, are able to enter and gather in tumor sites [45].
Even though most of the drug delivery methods are focused on cancer treatments, some specialize in other problematic areas of the human body. Skin is the largest organ of the body and the stratum corneum is the main barrier that drugs need to penetrate to get into the deeper layer of the skin. In the case of antifungals, drugs should be able to get through this layer but are not always able to do so. The development of nanosized colloidal carriers can be used as vehicles for drug delivery. Studies done on naftifine‐loaded microemulsion colloidal carriers showed that the carriers were an effective way of delivering naftifine, an antifungal drug, to deeper layers of the skin. Additionally, the method of delivery was shown to have low levels of cytotoxicity [46].
1.2.3 Biosensors
Biosensors are tools used to detect and analyze biological elements. Conventional biosensors have their advantages, but they also exhibit several limitations. Nanotechnology, however, eliminates the limitations of conventional methods. In fact, as the material dimensions are minimized, the applicability of biosensors is improved [47]. There are several nanoparticle‐based biosensors that can help detect pathogenic viruses. For example, the development of quantum dots‐based imaging and capturing systems for selective capturing and detection of the HIV in whole blood. It is a dual‐stain imaging system for the detection of HIV1 gp120 envelope glycoprotein. It is also capable of obtaining countable imaging. This system can work with 10 μl of a blood sample, is portable, and is highly cost‐effective compared to other methods [48]. For the detection of multiple viruses, the fluorescence characteristic of AgNPs is quite useful for optical biosensors. Using silver nanoclusters, biosensors have been prepared for the detection of specific DNA sequences of HIV, hepatitis B virus (HBV) and human T‐lymphotropic virus type I (HTLV‐I) gene. Before binding to the DNA sequence, these nanoclusters exhibited high fluorescence activity. After attaching to the sequence, however, the fluorescence intensity decreased, allowing the target sequences to be detected [49]. Additionally, magnetic nanoparticles have also been utilized for virus detection. Amino functional carbon‐coated magnetic nanoparticles, for example, have been used to distinguish hybridization of HBV nucleic acids [50, 51].
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by inhibiting translation and play a role in RNA degradation [52–54]. Currently, miRNA detection has several limitations such as sensitivity and selectivity [55]. Additionally, the current methods of miRNA detection, including northern blotting, microarray analysis, and RT‐PCR, are high in cost, complicated to handle, and do not produce stable results [56]. Tumor‐derived miRNA‐141 deregulation in human plasma is an important biomarker for blood‐based detection of various cancers, such as prostate [57], colons [58], and ovarian [59]. An electrochemical immunosensor composed of modified gold electrodes, reduced graphene oxide, and CNTs has been developed for the detection of the miR‐141 gene. With this method, the detection limit was down to 10fM [60]. Similar to miRNA‐141, miRNA‐155 is another biomarker for diagnosis of diffuse large B‐cell lymphoma [61]. Oligo‐hybridization‐based electrochemical biosensors can be used for its detection. These biosensors utilized GNPs on sheets of graphene oxide situated on glassy carbon electrodes. This particular biosensor
